Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine
Authors: Ehsan Mostafavi, Sana Eybpoosh, Mohammad Karamouzian, Malahat Khalili, Saiedeh Haji-Maghsoudi, Mostafa Salehi-Vaziri, Ali Khamesipour, Tahmineh Jalali, Mehran Nakhaeizadeh, Hamid Sharifi, Yasaman Mansoori, Fariba Keramat, Samad Ghodrati, Mostafa Javanian, Delaram Doroud, Mir Davood Omrani, Hassan Asadi, Mohammad Hassan Pouriayevali, Roya Ghasemian, Hossein Farshidi, Morteza Pourahmad, Iman Ghasemzadeh, Leila Mounesan, Maryam Darvishian, Mohamad Reza Mirjalili, Maria Eugenia Toledo-Romani, Carmen Valenzuela-Silva, Vicente Verez-Bencomo, Mohammad Mehdi Gouya, Hamid Emadi-Koochak, Ali Akbar Haghdoost, Alireza Biglari, Behnaz Soleimani Tappeh Sari, Soheil Ebrahimpour, Rostam Heydar Tabar, Roghayye Vaseghi, Bahram Mirzaei, Mehdi Safarpour, Farzin Sadeghi, Mahmoud Hosseinpoor, Tayebeh Raznahan, Leila Haddadi, Arezoo Mobarak Abadi, Elham Khalili, Mehrsa Manaei, Hassan Morshedi, Hamed Gooklani, Manouchehr Karami, Mohammad  Khazaei, Seyyed Jalaleddin Bathaei, Ali Ataei, Ali Zahiri, Zahra  Eskandari, Firouzeh Karbalaei Zadeh, Elham Abdoli, Marzieh Arjmandian, Maryam Zamanian, Razieh Sadat Mirmoeini, Seyyede Zeinab Hashemi, Farid Azizi Jalilian, Kamal Heidari, Mehdi Farsi, Mahnaz Mostajeran, Marjan Mashkooti, Somayye Davashi, Nastaran Kian Poor, Asefeh Haddadpour, Fariba Mazrooei, Hossein Safizadeh, Mohammadreza Naghavi, Saeed Sohbati, Nadia Mohit Kermani, Nasim Nasiri Moghaddam, Shahriar Dabiri, Ghasem Oveis, Mohammadreza Parsaei, Maghsood Khalizadeh, Abbas Arjmand, Fatemeh Yazdi Zadeh, Hadi Dehbashi araghdari, Zainab Bandalizadeh, Mohammadreza Dehghani, Mehrdad Mansouri, Masoud Sharifi, Hossein Shojaei Far, Javad Soheili, Sina Owlia, Masoumeh Mazidi, Mohammad Sharif Yazdi, Mahdieh Bahri, Razieh Sadat Hashemi, Alireza Talebi, Saeideh Anvari, Ahmad Jafari, Mohammadreza Saeini, Fariba Najafi, Davoud Rahmani, Ali Seidy, Mahshid Hajikhani, Hossein Dinmohammadi, Amir Javadi, Seyed Ebrahim Eskandari, Farhad Handjani, Maryam Chegeni, Katayoun Seif Farahi, Payman Hemmati, Mahsa Tavakoli Rad, Zahra Fereidooni, Sahar Khakifirouz, Tahereh Mohammadi, Mehdi Fazlalipour, Ali Maleki, Amir Hesam Nemati, Ahmad Ghasemi, Sanam Azad Manjiri, Zahra Ahmadi, Parastoo Yekta Sanati, Setareh Kashanian, Mohammad Mehdi Mortazavipoor, Laya Farhan Asadi, Zahra Hosseini, Farideh Niknam Oskouei, Sepideh Gerdooie, Marzyie Sajadi, Maryam Rostamtabar, Talieh Sabouni, Alireza Rahimi, Alireza Kavianpour, Seyed Mohsen Zahraei, Katayoun Tayeri, Ali Asadollahi Amin, Hamid Reza  Tohidinik, Azam Rastegari, Soheil Mehmandoost
Journal: JAMA Network Open (2023)

Importance The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and Participants A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. Interventions In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and Measures The primary outcome was polymerase chain reaction–confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. Results In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. Conclusions and Relevance In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19–related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registration isrctn.org Identifier: IRCT20210303050558N1